Viral hepatitis resulting from a virus other than hepatitis A virus (HAV) and hepatitis B virus (HBV) has been referred to as non-A, non-B hepatitis (NANBH). One of these, known as enterically transmitted NANBH or ET-NANBH, is contracted predominantly in poor-sanitation areas where food and drinking water have been contaminated by fecal matter. The molecular cloning of the causative agent, referred to as the hepatitis E virus (HEV), has recently been described (Reyes et al. (1990); Tam et al.).
A second NANB virus type, known as parenterally transmitted NANBH, or PT-NANBH, is transmitted by parenteral routes, typically by exposure to blood or blood products. Although the rate varies by locale, approximately 10% of transfusions cause PT-NANBH infection, and about half of these go on to a chronic disease state (Dienstag). After anti-HCV testing, HCV seroconversion per unit transfused was decreased to less than 1% among heart surgery patients.
Human sera documented as having produced post-transfusion NANBH in human recipients have been used successfully to produce PT-NANBH infection in chimpanzees (Bradley). RNA isolated from infected chimpanzee sera has been used to construct cDNA libraries in an expression vector for immunoscreening with chronic-state human PT-NANBH serum. This procedure identified a PT-NANBH specific cDNA clone and the viral sequence was then used as a probe to identify a set of overlapping fragments making up 7,300 contiguous basepairs of a PT-NANBH viral agent. The sequenced viral agent has been named the hepatitis C virus (HCV) (for example, the sequence of HCV is presented in EPO patent application 88310922.5, filed Nov. 18, 1988). The full-length sequence (.about.9,500 nt) of HCV is now available.
Primate transmission studies conducted at the Centers for Disease Control (CDC; Phoenix, Ariz., 1973-1975; 1978-1983) originally provided substantial evidence for the existence of multiple agents of non-A, non-B (NANBH): the primary agents of NANB are now recognized as being associated with infection by HCV and HEV (see above). Later epidemiologic studies conducted at the CDC (Atlanta, Ga., 1989-present) using both research (prototype) and commercial tests for anti-HCV antibody showed that approximately 20% of all community-acquired non-A, non-B hepatitis was also non-C. Further testing of these samples for the presence of HEV (co-owned, co-pending U.S. application Ser. No. 07/372,711, filed 28 Jun. 1989, herein incorporated by reference) have indicated that these cases of community-acquired non-A, non-B, non-C hepatitis were also non-E.
Liver biopsy specimens of Sentinel County patients obtained during the last five years (study of Drs. Miriam Alter and Kris Krawcynski) also showed that many bona fide cases of NANBH were also non-C hepatitis (serologically and RT-PCR (Kawasaki, et al.; Wang, et al.) negative for all markers of HCV infection) developed subsequently into chronic hepatitis with presentation of chronic persistent hepatitis (CPH) or chronic active hepatitis (CAH) consistent with a viral infection.